The Cytoplasmic Tail of Rhodopsin Acts as a Sorting Signal in Polarized Photoreceptors and MDCK Cells

Abstract

In this report, we demonstrate that wild-type rhodopsin is targeted to the apical plasma membrane via the trans- Golgi network (TGN) upon expression in polarized epithelial Madin-Darby canine kidney (MDCK) cells. Truncated rhodopsin with a deletion of 32 C-terminal residues shows a non-polar steady-state distribution. Addition of the C-terminal 39 residues of rhodopsin redirects the basolateral membrane protein CD7 to the apical membrane. Fusion of rhodopsin’s cytoplasmic tail to a cytosolic protein glutathione 5-transferase (GST) also targets this fusion protein (GST-Rho39Tr) to the apical membrane. We conclude that the carboxy-terminal tail of rhodopsin contains a novel cytoplasmic apical sorting determinant. This result is in agreement with previous studies showing that the cytoplasmic tail of rhodopsin mediates its vectorial transport from its site of synthesis in the rod photoreceptor cell body to the rod outer segment, where phototransduction occurs. Several mutant rhodopsins, found in patients with autosomal dominant retinitis pigmentosa (ADRP), have an amino acid change at the carboxy-terminus and these mutants are defective in their outer segment localization. It will be of interest to examine the relationship between the defects in rhodopsin’s targetingJ.transport and the pathogenesis of retinal degeneration.

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